We are studying: (1) the mechanisms involved in the renal handling of lead; (2) the effects of lead on renal sodium handling, renin secretion, and erythropoietin secretion. Our basic findings to date are: (1) acutely administered lead is handled by a complex interaction of filtration, reabsorption, and secretion; (2) lead inhibits sodium reabsorption and stimulates renin secretion. In the coming year, we propose to study the following: (1) Further elucidation of the renal pathways for lead handling and the factors which influence them. We will study the effects of agents which block tubular secretion of organic anions (probenecid, PAH, non-active analogues of carbonic anhydrase) and which block tubular reabsorption of amino acids (maleic acid); we will study more closely acid-base effects on lead excretion. (2) Identification of the low-molecular-weight chelator for lead in plasma. (3) Validation of our atomic absorption methodology for lead in plasma ultrafiltrate. (4) Evaluation of renal lead handling in chronically lead-fed dogs. (5) Evaluation of renal electrolyte handling and hormone secretion during salt-loading, salt-deprivation, and various stimuli known to increase renin secretion. This will test the ability of the chronically lead-poisoned kidney to respond to stimuli. (6) Evaluation of the effects of vitamin D, thyrocalcitonin, and changes in plasma calcium on renal accumulation of lead. (7) Development of an in vitro renal-slice technique for evaluating lead accumulation and the effects of lead on the kidney.